Synthetic and naturally occurring cannabinoids are a focus of strong social, legal and medical controversy concerning their therapeutic utility, yet studies show that cannabinoids reduce the symptoms of hyperalgesia and allodynia associated with persistent pain of inflammatory and neuropathic origin in humans and animals. Furthermore, cannabinoids are effective in alleviating chronic pain symptoms after prolonged repeated treatment, unlike opioids, which have only limited effectiveness. A major impediment to the widespread use of cannabinoid analgesics has been their central nervous system (CNS)-mediated psychotropic side effects. In addition, there are various other conditions where selective activation (or blockade) of peripheral cannabinoid receptors could prove to be of clinical benefit.